Veterinary Surgery 32:515-523, 2003 The Effect of Topical Tripeptide-Copper Complex on Healing of Ischemic Open Wounds SHERMAN O. CANAPP JR, DVM, MS, JAMES P. FARESE, DVM, Diplomate ACVS, GREGORY S. SCHULTZ, PhD, SANTOSH GOWDA, MBBS, MS, ANTHONY M. ISHAK, DVM, STEVEN F. SWAIM, DVM, MS, JAMES VANGILDER, BS, LINDA LEE-AMBROSE, PhD, and FRANK G. MARTIN, PhD Objective—To evaluate the effects of topical glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA) on healing in ischemic open wounds. Study Design—Experimental study. Sample Population—Twenty-four adult male Sprague-Dawley rats. Methods—Rats were divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl- methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness wounds were created within an ischemic bipedicle skin flap on the dorsum of each rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC vehicle groups were treated topically. Tracings were scanned, and wound perimeter and area were calculated. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor  (TNF-) and matrix metalloproteinases (MMP) 2 and 9. Results—A significant decrease in wound area was seen in the TCC group, but not the vehicle group, when compared with the control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On days 6, 10, and 13, TCC-treated wounds contained significantly lower concentrations of TNF- and MMP-2 and MMP-9 than control wounds. Conclusion—Topical TCC resulted in accelerated wound healing in ischemic open wounds. Clinical Relevance—Topical TCC is an effective stimulant of healing of ischemic open wounds in rats and may have an application for the treatment of chronic wounds in other species. Clinical evaluation of topical TCC is warranted. © Copyright 2003 by The American College of Veterinary Surgeons C HRONIC WOUNDS pose a significant manage- ment challenge and can be debilitating to the patient, costly to manage, and difficult to resolve. In veterinary medicine, chronic wounds are most com- monly associated with trauma, neoplasia, pressure necrosis, radiation injury, burns, and indolent ulcers. Approaches to managing chronic wounds usually in- cludes reducing tissue trauma, ischemia, and bacterial contamination as well as the application of therapeutic dressings and the use of growth factors for their potential to stimulate chronic, nonhealing wounds into an active state of healing. 1 The molecular environment of chronic wounds includes elevated concentrations of tumor necrosis factor  (TNF-), matrix metalloproteinases (MMP; MMP-2 and MMP-9), and serine proteinases. 2-4 These From the Department of Small Animal Clinical Sciences and the Department of Statistics, University of Florida College of Veterinary Medicine, and the School of Medicine Institute for Wound Research, Gainesville, FL; and the College of Veterinary Medicine Scott-Ritchey Research Center, Auburn, AL. Presented at the American College of Veterinary Surgeons Annual Meeting, San Diego, CA, October 2002. No reprints available. Address correspondence to James P. Farese, DVM, University of Florida College of Veterinary Medicine, Gainesville, FL 32610. © Copyright 2003 by The American College of Veterinary Surgeons 0161-3499/03/3206-0003$30.00/0 doi:10.1053/jvet.2003.50070 515